Jump to

Abstract

Background Shear stress increases the expression of tissue-type plasminogen activator (t-PA) in endothelial progenitor cells (EPCs. However, the underlying mechanism responsible for the shear stress-stimulated t-PA expression of EPCs is not clear. Here, we investigated the role of mitogen-activated protein kinases (MAPK) and nuclear factor (NF-kB) signaling in shear stress-induced upregulation of t-PA expression in EPCs.

Methods and Results The human EPCs were treated with four levels of laminar shear stress including stationary condition,low (5 dyn/cm2),media (15 dyn/cm2) and high (25 dyn/cm2) laminar shear stress. Shear stress, in a dose-dependent manner, increased t-PA secretion and protein expression of human EPCs. When exposed to 15 dyn/cm2 laminar shear stress, the phosphorylation of extracellular signal-related kinase (ERK)1/2 and c-Jun N-terminal protein kinase (JNK) of human EPCs were activated from 12 to 24 hours. In parallel, 15 dyn/cm2 laminar shear stress increased the phosphorylation of p38 and NF-kB of human EPCs from 6 to 24 hours. However, 5 dyn/cm2 shear stress had no effect on the phosphorylation of ERK1/2, JNK, p38 and NF-kB of human EPCs. After ERK1/2 and Raf inhibition, the effects of shear stress on the protein and gene expression of t-PA in human EPCs were inhibited.

Conclusions The present findings demonstrate for the first time that shear stress-induced activation of Raf/MEK/ERK1/2 signaling pathway contributes to upregulation of t-PA expression in human EPCs.